Evolution Is Condemned to Rely upon Variations of the Same Theme: The One Ancestral Sequence for Genes and Spacers

EVOLUTION IS CONDEMNED TO RELY UPON VARIATIONS OF THE SAME THEME: THE ONE ANCESTRAL SEQUENCE FOR GENES AND SPACERS SUSUMU OHNO* The "kappa" is a mythological humanoid species ofJapanese folklore whose frolics are as likable as those of "hobbits" in J. R. R. Tolkien's tales. It is said that when a female kappa becomes pregnant, the sacred duty befalls a prospective father to inform an emerging embryo about its parental pedigrees, social stations, and financial statuses. He does so by using the female's expanded vagina as a megaphone. Upon digesting the informationjust received, an embryo conveys its decision to the parents about whether to be born or to be aborted. Because of the immutably postnatal development of human comprehension, man is forever denied this ultimate freedom of choice. As far as the genetic constitution, which assuredly is one's most important asset as well as liability, is concerned, man is destined to be a slave of fate and never its master. The soon-tobe -acquired ability to manipulate human embryonic DNA makes no difference , for the manipulation of one's own genome can only be done by one's predecessors, never by oneself. As to the nature and limit of human genetic constitution, that is, human intelligence, I was struck by the profoundness of the following statement that I found in one of the writings of Vladimir Nabokov: "While ordinary mortals are content to imitate others, creative persons are condemned to plagiarize themselves." Indeed, the lifework of each great composer , painter, novelist, and scientist can usually be construed as many variations of the one invented theme. This revealing limitation in human intelligence is no surprise, for during the past 20 years, we have learned that the evolutionary process itself is very seldom inventive, most of the time being content to rely on variations of the old and tested theme. Work supported by NIH grant ROl ATT5620 and grants from Wakunaga Pharmaceutical Co. and Nomura Research Institute ofJapan. ?Division of Biology, City of Hope Research Institute, Duarte, California 91010.© 1982 by The University of Chicago. AU rights reserved. 003 1 -5982/82/2504-0300$0 1 .00 Perspectives in Biology and Mediane, 25, 4 ¦ Summer 1982 | 559 Indeed, what at the first glance appeared as a new gene invariably proved itself as a mere modified derivative of the old. Since these modified derivatives arose from redundant copies of the old gene, the mechanism of gene duplication played the major evolutionary role [I]. For example, numerous polypeptide hormones of higher vertebrates can first be grouped to different families by the propinquity of their descents (e.g., insulin, relaxin, and somatomedins belong to one family, while glucagon and secretin belong to another [2]). Yet, the ultimate ancestry of all these polypeptide hormones can be traced back to digestive enzymes of the gut [3]. In this essay, I shall advance the view that all the genes and intergenic spacers in the vertebrate genome have ultimately originated from repeats of the one primordial sequence: (AGCTG) (AGCTG) (AGCTG) (GGGTG). Genes as Oases in a Barren Stretch ofDesert The genome size of diverse mammalian species including man is fairly uniform, being represented by roughly 3.2 x 109 BP (base-pairs) of DNA. The enormity of this genome size can be visualized by realization that twice the above amount of DNA contained in a diploid nucleus measures 1.3 cm in length. Yet the total number of functioning gene loci contained in this genome cannot be as enormous, for the simple reason that an organism has to pay a certain toll for the privilege of maintaining each gene locus [4]. It is in the fate of genes to be afflicted by randomly sustained mutations from time to time. Were it not for the ruthless vigilance by natural selection that weeds out a certain fraction of these mutations as deleterious, a gene would soon join the rank of nonsense DNA sequences. Thus, the deleterious mutation rate is a toll. It follows then that the possession of too many gene loci leads to the extermination of organisms from an unbearably high overall deleterious mutation rate, a number of deleterious mutations causing most of the embryos to die...